Visceral Leishmaniasis is an important parasitic infection of man whose pathogenesis depends on intracellular parasitism of host macrophages by amastigotes. The initial interface between parasites and host cells occurs at the plasma membrane and recent attention has focussed on host-parasite membrane interactions. Of particular importance is the identification of attachment sites for amastigotes on macrophages since it would permit the design of inhibitors of organism adherence and entry into host cells. Similarly, characterization of parasite induced modifications of the macrophage plasma membrane may provide an important immunodiagnostic reagent and help select the appropriate antigens for vaccine development. However models employing intact macrophages for the study of parasite-host cell membrane interactions have distinct limitations. Methodologic advances in the laboratories of the investigators in this proposal provide a unique opportunity to study amastigote-macrophage membrane interactions. We have successfully isolated macrophage plasma membrane vesicles and have developed an in vitro culture system for human macrophages infected with species of Leishmania pathogenic to man. Application of these new techniques should allow us to investigate the nature of parasite receptors on the surface of macrophages as well as determine parasite-induced alteration in macrophage composition.